BACKGROUND: Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling. METHODS: We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted. RESULTS: We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another. CONCLUSION: Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.
BACKGROUND:Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling. METHODS: We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted. RESULTS: We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another. CONCLUSION: Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.
Authors: Bart L T Vaes; Koen J Dechering; Eugene P van Someren; José M A Hendriks; Cindy J J M van de Ven; Alie Feijen; Christine L Mummery; Marcel J T Reinders; Wiebe Olijve; Everardus J J van Zoelen; Wilma T Steegenga Journal: Bone Date: 2005-04-07 Impact factor: 4.398
Authors: Karen Kapur; Toby Johnson; Noam D Beckmann; Joban Sehmi; Toshiko Tanaka; Zoltán Kutalik; Unnur Styrkarsdottir; Weihua Zhang; Diana Marek; Daniel F Gudbjartsson; Yuri Milaneschi; Hilma Holm; Angelo Diiorio; Dawn Waterworth; Yun Li; Andrew B Singleton; Unnur S Bjornsdottir; Gunnar Sigurdsson; Dena G Hernandez; Ranil Desilva; Paul Elliott; Gudmundur I Eyjolfsson; Jack M Guralnik; James Scott; Unnur Thorsteinsdottir; Stefania Bandinelli; John Chambers; Kari Stefansson; Gérard Waeber; Luigi Ferrucci; Jaspal S Kooner; Vincent Mooser; Peter Vollenweider; Jacques S Beckmann; Murielle Bochud; Sven Bergmann Journal: PLoS Genet Date: 2010-07-22 Impact factor: 5.917
Authors: Anatoliy I Yashin; Ilya Zhbannikov; Liubov Arbeeva; Konstantin G Arbeev; Deqing Wu; Igor Akushevich; Arseniy Yashkin; Mikhail Kovtun; Alexander M Kulminski; Eric Stallard; Irina Kulminskaya; Svetlana Ukraintseva Journal: Front Genet Date: 2016-11-08 Impact factor: 4.599